The observation that F1 hybrid murine lymphocytes respond to parental lymphoid cells in one-way lymphocyte culture would seem to conflict with the fact that parental skin grafts are not rejected by F1 animals. An explanation for this paradoxical situation will be sought. Experiments will be conducted to determine whether subsets of F1 lymphocyte populations react to one or both parental histocompatibility antigen complexes. This will be tested in several ways. F1 cells responsive to one set of parental antigens will be eliminated and the remaining cells tested for reactivity to the other set of parental antigens. We have preliminary evidence that separate sub-populations are involved. Using several lines of congenic mice and their F1 hybrids, studies will then be performed to test whether F1 recognition of parent in vitro is linked to the histocompatibility gene complex or is due to some other, not currently identified locus. An hypothesis which predicts that allelic exclusion occurs in thymus-derived lymphocytes and is the mechanism responsible for the mixed lymphocyte culture reactivity between F1 and parental cells will be tested. BIBLIOGRAPHIC REFERENCES: Gebhardt, B.M. 1975. Fl hybrid lymphocyte recognition of parental cells in one-way mixed lymphocyte cultures. Fed. Proc. 34:1028 (abstract).